The invention relates to the field of hematology and immunology.
Antigens encoded by the murine Ly-6 gene family were originally identified as alloantigens. These antigens are expressed in both hematopoietic and non-hematopoietic tissues (Shevach, E., Immunology Today; Rock et al., 1989 Immunol. Rev. 3:195). The murine Ly-6 locus contains DNA sequences for at least four distinct genes (Fleming, 1993), e.g., Ly-6A, Ly-6C, Ly-F, and Ly6-G, and each gene is characterized by a unique pattern of tissue expression.
Common features shared by members of the murine Ly-6 gene family include: phosphatidylinositolglycan-linkage to the plasma membrane (Williams, A., 1991 Cell Bio. Int Rep, 15:769-777; Rock et al., 1989, Immunol. Rev. 3:195), interferon (IFN) inducibility (Dumont, F. and Coker, L., 1986 Eur. J. Immunol. 16:735-740; Dumont et al. 1987, Eur. J. Immunol. 17:1183-1191), and a predicted protein structure similar to .alpha.-bungarotoxin (Fleming et al., 1993, J. Immunol. 150:5379-5390). These proteins also have a characteristic pattern of 8-10 highly conserved cysteine residues and the predicted formation of .beta.-sheet structure. The existence of other proteins which possess similar structural characteristics, yet sharing little DNA sequence homology, may suggest the emergence of a family of structurally-related proteins.
The murine antigen, Sca-1, was first defined on murine bone marrow cells and later shown to be identical to murine Ly-6A.2 (Van de Rijn et alo, 1989, Proc. Natl. Acad. Sci. USA 86:4634-4638). Antibodies to the murine stem cell antigen, Sca-1, have been shown to identify a population of cells enriched in hematopoietic stem cells (Spangrude, G. et al., 1988, Science, 241:58-62; Spangrude, G. et al., 1992 Blood 80:1957-1964).
For human therapy, the isolation of pure hematopoietic stem cells is beneficial for treatments, such as bone marrow transplants. Procedures to isolate pure stem cells are problematic and inefficient due in part to a lack of reliable cell surface markers. Present protocols for isolation of human hematopoietic stem cells rely heavily on stem cell expression of the CD34 antigen (Terstappen et al., 1991, Blood 77:1218-1227) and in some instances by CD34 and Thy-1 expression (Baum, C. M., 1992, Proc. Natl. Acad. Sci. USA 89:2804-2808), however contamination with undesirable cells remains a problem.